瑞芬太尼缓解氧化应激对内毒素诱导的SD大鼠急性肺损伤的保护作用

Remifentanil attenuates lipopolysaccharide-induced acute lung injury by alleviating oxidative stress

目的:探究瑞芬太尼对大鼠急性肺损伤(ALI)的作用及作用机制。方法:腹腔注射脂多糖(LPS)复制大鼠ALI模型,并于造模前1 h尾静脉注射瑞芬太尼或生理盐水进行预处理。用TUNEL检测细胞凋亡情况,免疫组化检测Ki67及Caspase-3的含量,ELISA检测血清炎症因子浓度,试剂盒检测MDA和SOD浓度; Western blot法检测PI3K/AKT通路蛋白表达。结果:瑞芬太尼能显著抑制肺组织细胞凋亡及Caspase-3的表达(P<0. 05),并促进Ki67的表达(P<0. 05);同时,瑞芬太尼还可明显降低ALI血清炎症因子(IL-6、IL-1β、IFN-γ)及MDA含量(P<0. 05),并能显著促进SOD的分泌(P<0. 05);此外,瑞芬太尼还可显著降低p-PI3K/PI3K和p-AKT/AKT的比值(P<0. 05)。结论:瑞芬太尼可通过缓解炎症反应和氧化应激减轻ALI大鼠肺损伤,其机制可能与抑制PI3K/AKT信号通路激活有关。

Objective:To evaluate the effects of remifentanil on lipopolysaccharide(LPS)-induced acute lung injury in rats.Methods:The ALI model was induced by LPS and rats were treated with remifentanil or saline.Rats were sacrificed and cell apoptosis was measured by TUNEL assay.The expression of Ki67 and Caspase-3 were detected by immunohistochemistry.ELISA assay was performed for inflammatory cytokines and the concentrations of MDA and SOD also was measured.The protein levels were calculated by Western blot.Results:Remifentanil inhibited apoptosis and the expression of Caspase-3 coupled with increasing Ki67(P<0.05).Meanwhile,remifentanil decreased the contents of serum inflammatory cytokines(IL-6,IL-1β,IFN-γ)and MDA(P<0.05),and increased the secretion of SOD(P<0.05).In addition,remifentanil activated PI3K/AKT pathway as demonstrated by decreasing ratio of p-PI3K/PI3K and p-AKT/AKT(P<0.05).Conclusion:Remifentanil alleviates ALI of rats through inhibiting inflammation and oxidative stress,and the mechanism may be related with PI3K/AKT signaling pathway.